ARCHIVED - Glyphosate Tolerant Soybean

Novel Food Information - Herbicide Tolerant Soybean Event 356043

Health Canada has notified Pioneer Hi-Bred Production Ltd. that it has no objection to the food use of Herbicide Tolerant Soybean Event 356043. The Department conducted a comprehensive assessment of this soybean event according to its Guidelines for the Safety Assessment of Novel Foods. These Guidelines are based upon internationally accepted principles for establishing the safety of foods with novel traits.

Background:

The following provides a summary of the notification from Pioneer Hi-Bred Production Ltd. and the evaluation by Heath Canada and contains no confidential business information.

1. Introduction

Soybean event 356043 (tradename Optimum GAT) was genetically modified using recombinant DNA techniques to introduce the coding sequences and associated regulatory sequences for a novel glyphosate acetyltransferase variant (gat4601) and an acetolactate synthase (ALS) from Glycine max (gm-hra). The gat4601 sequence codes for a novel glyphosate acetyltransferase, a variant of the native Bacillus licheniformis enzyme, which acetylates the herbicidal active ingredient glyphosate in the presence of acetyl-CoA. The gm-hra sequence codes for an acetolactate synthase, which catalyses the first step in the synthesis of the branched-chain amino acids (valine, leucine, and isoleucine). Expression of the GAT4601 and GM-HRA proteins confers tolerance to ALS-inhibiting herbicides and herbicides containing glyphosate in soybean event 356043.

The assessment conducted by Food Directorate evaluators determined: how soybean event 356043 was developed; how the composition and nutritional quality of soybean event 356043 compared to non-modified varieties; and what the potential is for event 356043 soybeans to be toxic or cause allergic reactions. Pioneer Hi-Bred Production has provided data which demonstrates that event 356043 soybeans are as safe and of the same nutritional quality as traditional soybean varieties used as food in Canada with the exception of a nominal increase in two fatty acids (heptadecanoic acid and heptadecenoic acid), and the presence of five acetylated amino acids (N-acetylaspartate, N-acetylglutamate, N-acetylserine, N-acetylthreonine, and N-acetylglycine). The two fatty acids do not pose a nutritional concern and are readily metabolized within the body. Acetylated amino acids are present in a wide variety of foods. Furthermore, the levels of acetylated threonine, serine, and glycine in soybean event 356043 are comparable to the conventional soybean cultivar Jack.

The Food Program has a legislated responsibility for the pre-market assessment of novel foods and novel food ingredients as detailed in the Food and Drug Regulations (Division 28). Food use of soybean event 356043 is considered novel under the following part of the definition of novel foods:

"c) a food that is derived from a plant, animal or microorganism that has been genetically modified such that

(I) the plant, animal or microorganism exhibits characteristics that were not previously observed in that plant, animal or microorganism."

2. Development of the Modified Plant

Soybean event 356043 was genetically modified using biolistic transformation of soybean embryo tissue with a gel-purified restriction DNA fragment consisting of the gat4601 and gm-hra genes and their associated regulatory sequences from plasmid vector PHP20163. The purified fragment, designated PHP20163A, is composed of a constitutive synthetic promoter sequence comprising a portion of the CaMV 35S promoter and the Rsyn7-Syn II Core consensus promoter (P-SCP1), the Tobacco Mosaic Virus (TMV) omega 5 untranslated region leader sequence (5 UTR-TMV omega), the synthetic glyphosate N-acetyltransferase (gat) gene (gat4601), the terminator region from Solanum tuberosum proteinase inhibitor II (pinII) gene (T-pinII), the promoter sequence of the soybean S-adenosyl L-methionine synthetase (P-SAMS), the 5 untranslated region of the soybean SAMS gene (5 UTR-SAMS) flanking an intron (I-SAMS), a modified version of the acetolactate synthase gene from soybean (gm-hra), and the terminator region of the acetolactate synthase gene from soybean (T-gm-als).

Expression of the GAT4601 protein from the inserted gat4601 gene confers tolerance to the active ingredient glyphosate by acetylating glyphosate, thereby rendering it non-phytotoxic. Introduction of the gm-hra gene encodes for the GM-HRA protein, a modified version of a soybean acetolate synthase conferring tolerance to the ALS-inhibiting class of herbicides. Successfully transformed soybean embryo tissues were selected on media containing ALS-inhibiting herbicide, and the presence of the gat4601 and gm-hra transgenes was confirmed by Southern blot analysis.

3. Characterization of the Modified Plant

Southern blot analysis and DNA sequencing of soybean event 356043 demonstrated the presence of a single copy of the PHP20163A DNA fragment the soybean genome at a single locus. The insertion fragment is composed of intact copies of the gat4601 and gm-hra gene cassettes. Southern blot analysis confirmed the absence of any plasmid backbone DNA in soybean event 356043.

The stability of the inserted gat4601 and gm-hra cassettes was evaluated from the progeny of five different generations. The results of Southern blot analysis and segregation data demonstrated the stability of the soybean event 356043 at the genomic level.

4. Product Information

Soybean event 356043 differs from its traditional counterpart by the addition of the gat4601 and gm-hra gene sequences and their respective regulatory elements. Introduction of the gat4601 gene encodes for the GAT4601 protein, a novel glyphosate acetyltransferase conferring tolerance to herbicides containing glyphosate. Introduction of the gm-hra gene encodes for the GM-HRA protein, a modified version of a soybean acetolate synthase conferring tolerance to ALS-inhibiting herbicides.

5. Dietary Exposure

Soybean event 356043 is expected to be used in similar applications as other soybean and vegetable oils by the food industry.

6. Nutrition

The nutrient data pertaining to herbicide tolerant soybean event 356043 were obtained from two studies. The first study compared the nutrient composition of grain derived from the transgenic soybean event 356043 and the non-transgenic soybean cultivar (Jack). The second study was conducted to determine the nutrient composition of four commercial non-transgenic soybean varieties in order to generate reference values.

The grain samples were collected from six sites in the United States and Canada and analyzed for proximates, 18 amino acids, 24 fatty acids, 8 minerals, sodium, 4 vitamins, 12 isoflavones, 3 oligosaccharides, and 4 secondary metabolites and anti-nutrients.

The chemical and nutritional composition of the soybean from transgenic and non-transgenic samples was comparable. Significant differences that were observed did not raise any nutritional concerns.

Significant differences were observed for two fatty acids: heptadecanoic and heptadecenoic acid. The nominal increases of these two components from the transgenic soybean event 356043 did not pose as a nutritional concern as both fatty acids are readily metabolized in the body. Elevated levels of five acetylated amino acids (N-acetylaspartate, N-acetylglutamate, -acetylserine, N-acetylthreonine, and N-acetylglycine) were also present in the transgenic soybean event 356043. Information was provided to support that humans and other mammals possess aminoacetylase enzymes in various tissues (brain, kidney, liver, intestine). It was reported that acetylated amino acids are present in a wide variety of foods, including non-transgenic soybeans. The levels of N-acetylserine, N-acetylthreonine, and N-acetylglycine in transgenic soybean event 356043 were within tolerance intervals established from representative conventional soybeans.

A 42-day broiler chicken feeding study was conducted using diets containing either transgenic soybean event 356043 or its non-transgenic soybean cultivar (Jack). No significant differences were found in any of the standard parameters assessed.

7. Chemistry/Toxicology

The gat4601 gene present in soybean event 356043 is a synthetic construct based on N-acetyltransferase protein sequences from Bacillus licheniformis. Defined as a Class I microorganism by the National Institutes of Health (NIH), B. licheniformis has no known history of causing disease in humans or animals The gm-hra gene present in soybean event 356043 was also isolated from a non-pathogenic source (soybean; Glycine max).

GAT4601 and GM-HRA are not considered likely to be toxins, due to the absence of acute toxicity observed for mice fed by gavage each protein at doses orders of magnitude greater than the range typically associated with toxic proteins. Both novel proteins bear no biologically significant homology to any known mammalian toxin.

Neither GAT4601, nor GM-HRA protein are considered likely to be an allergen since neither possesses the characteristics of proteins that are food allergens. Unlike many food allergens, these novel proteins constitute a negligible amount of the total protein in the transgenic soybean event 356043. Both proteins are rapidly degraded in simulated gastric fluid and simulated intestinal fluid systems, as detected by Western blot analysis. These results suggest that these novel proteins would be digested in the mammalian digestive tract. In addition, both GAT4601 and GM-HRA are completely inactivated at 56 and 50 degrees Celsius respectively. Neither novel protein is glycosylated, a common attribute of known allergens.

In terms of endogenous allergen content, soybean event 356043 is not significantly different from that of the conventional soybean cultivar Jack. Evidence from an ELISA inhibition assay demonstrated that protein extracts derived from 356043 exhibit no significant difference compared to the conventional counterpart in their ability to bind IgE present in the pooled sera from soy allergic patients.

The production of N-acetylglyphosate, in addition to the acetylation of unintended substrates was addressed for soybean event 356043. A 90-day study of rats fed N-acetylglyphosate at dietary levels of 18,000 ppm concluded with no adverse effects observed. Results indicated the majority of N-acetylglyphosate was excreted unaltered in the urine and therefore did not accumulate in the body. With regard to the acetylation of unintended substrates, five amino acids showed low but measurable affinity for the GAT4601 enzyme. Only levels of N-acetylaspartate and N-acetylglutamate are significantly increased in soybean event 356043. As deacetylase enzymes are widely distributed throughout the tissues (including brain, kidney, liver, and intestine), the presence of these acetylated amino acids did not raise a toxicological concern. Furthermore, acetylated amino acids are present in a variety of conventional foods.

Conclusion:

Health Canada's review of the information presented in support of the food use of Herbicide Tolerant Soybean Event 356043 does not raise concerns related to food safety. Health Canada is of the opinion that food derived from 356043 soybeans is as safe and nutritious as food from current commercial soybean varieties.

Health Canada's opinion deals only with the food use of soybean event 356043. Issues related to its use as animal feed have been addressed separately through existing regulatory processes in the Canadian Food Inspection Agency (CFIA). The CFIA evaluated information provided on the environmental, animal, and human health safety of soybean event 356043 with the intended use in animal feed. From their assessment, the CFIA concluded that there are no concerns from an environmental safety perspective. This perspective is applicable to the food and feed products derived from soybean event 356043 destined for commercial sale.

This Novel Food Information document has been prepared to summarize the opinion regarding the subject product provided by the Food Directorate, Health Products and Food Branch, Health Canada. This opinion is based upon the comprehensive review of information submitted by the petitioner according to the Guidelines for the Safety Assessment of Novel Foods.

(Également disponible en français)

For further information, please contact:

Office of Food Biotechnology
Food Directorate
Health Products and Food Branch
Health Canada
Tunney's Pasture
Ottawa, Ontario K1A 0L2
Telephone: (613) 941-5535
Facsimile: (613) 952-6400

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